Adipose tissue mitochondrial capacity associates with long-term weight loss success

R. Jokinen, R. Rinnankoski-Tuikka, S. Kaye, L. Saarinen, S. Heinonen, M. Myöhänen, E. Rappou, S. Jukarainen, A. Rissanen, A. Pessia, V. Velagapudi, K. A. Virtanen, E. Pirinen, K. H. Pietiläinen

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Sammanfattning

OBJECTIVES:

We investigated whether (1) subcutaneous adipose tissue (SAT) mitochondrial capacity predicts weight loss success and (2) weight loss ameliorates obesity-related SAT mitochondrial abnormalities.
METHODS:

SAT biopsies were obtained from 19 clinically healthy obese subjects (BMI 34.6±2.7 kg/m2) during a weight-loss intervention (0, 5, and 12 months) and from 19 lean reference subjects (BMI 22.7±1.1 kg/m2) at baseline. Based on one-year weight loss outcome, the subjects were divided into two groups: continuous weight losers (WL, n=6) and weight regainers (WR, n=13). Main outcome measures included SAT mitochondrial pathways from transcriptomics, mitochondrial amount (mitochondrial DNA (mtDNA), Porin protein levels), mtDNA-encoded transcripts, oxidative phosphorylation (OXPHOS) proteins, and plasma metabolites of the mitochondrial branched-chain amino acid catabolism (BCAA) pathway. SAT and visceral adipose tissue (VAT) glucose uptake was measured with positron emission tomography.
RESULTS:

Despite similar baseline clinical characteristics, SAT in the WL group exhibited higher gene expression level of nuclear-encoded mitochondrial pathways (P=0.0224 OXPHOS, P=0.0086 tricarboxylic acid cycle, P=0.0074 fatty acid beta-oxidation and P=0.0122 BCAA), mtDNA transcript COX1 (P=0.0229) and protein level of Porin (P=0.0462) than the WR group. Many baseline mitochondrial parameters correlated with weight loss success, and with SAT and VAT glucose uptake. During weight loss, the nuclear-encoded mitochondrial pathways were downregulated, together with increased plasma metabolite levels of BCAAs in both groups. MtDNA copy number increased in the WR group at 5 months (P=0.012), but decreased to baseline level between 5 to 12 months (P=0.015). The only significant change in the WL group for mtDNA was a reduction between 5 and 12 months (P=0.004). The levels of Porin did not change in either group upon weight loss.
CONCLUSIONS:

Higher mitochondrial capacity in SAT predicts good long-term weight loss success. Weight loss does not ameliorate SAT mitochondrial downregulation and based on pathway expression, may paradoxically further reduce it.
DATA AVAILABILITY:

The transcriptomics data generated in this study have been deposited to the Gene Expression Omnibus public repository, accession number GSE103769.
Originalspråkengelska
TidskriftInternational Journal of Obesity
Volym42
Utgåva4
Sidor (från-till)817-825
Antal sidor9
ISSN0307-0565
DOI
StatusPublicerad - apr 2018
MoE-publikationstypA1 Tidskriftsartikel-refererad

Vetenskapsgrenar

  • 3121 Inre medicin
  • 3111 Biomedicinska vetenskaper
  • 3124 Neurologi och psykiatri

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title = "Adipose tissue mitochondrial capacity associates with long-term weight loss success",
abstract = "OBJECTIVES:We investigated whether (1) subcutaneous adipose tissue (SAT) mitochondrial capacity predicts weight loss success and (2) weight loss ameliorates obesity-related SAT mitochondrial abnormalities.METHODS:SAT biopsies were obtained from 19 clinically healthy obese subjects (BMI 34.6±2.7 kg/m2) during a weight-loss intervention (0, 5, and 12 months) and from 19 lean reference subjects (BMI 22.7±1.1 kg/m2) at baseline. Based on one-year weight loss outcome, the subjects were divided into two groups: continuous weight losers (WL, n=6) and weight regainers (WR, n=13). Main outcome measures included SAT mitochondrial pathways from transcriptomics, mitochondrial amount (mitochondrial DNA (mtDNA), Porin protein levels), mtDNA-encoded transcripts, oxidative phosphorylation (OXPHOS) proteins, and plasma metabolites of the mitochondrial branched-chain amino acid catabolism (BCAA) pathway. SAT and visceral adipose tissue (VAT) glucose uptake was measured with positron emission tomography.RESULTS:Despite similar baseline clinical characteristics, SAT in the WL group exhibited higher gene expression level of nuclear-encoded mitochondrial pathways (P=0.0224 OXPHOS, P=0.0086 tricarboxylic acid cycle, P=0.0074 fatty acid beta-oxidation and P=0.0122 BCAA), mtDNA transcript COX1 (P=0.0229) and protein level of Porin (P=0.0462) than the WR group. Many baseline mitochondrial parameters correlated with weight loss success, and with SAT and VAT glucose uptake. During weight loss, the nuclear-encoded mitochondrial pathways were downregulated, together with increased plasma metabolite levels of BCAAs in both groups. MtDNA copy number increased in the WR group at 5 months (P=0.012), but decreased to baseline level between 5 to 12 months (P=0.015). The only significant change in the WL group for mtDNA was a reduction between 5 and 12 months (P=0.004). The levels of Porin did not change in either group upon weight loss.CONCLUSIONS:Higher mitochondrial capacity in SAT predicts good long-term weight loss success. Weight loss does not ameliorate SAT mitochondrial downregulation and based on pathway expression, may paradoxically further reduce it.DATA AVAILABILITY:The transcriptomics data generated in this study have been deposited to the Gene Expression Omnibus public repository, accession number GSE103769.",
keywords = "3121 Internal medicine, 3111 Biomedicine, 3124 Neurology and psychiatry",
author = "R. Jokinen and R. Rinnankoski-Tuikka and S. Kaye and L. Saarinen and S. Heinonen and M. My{\"o}h{\"a}nen and E. Rappou and S. Jukarainen and A. Rissanen and A. Pessia and V. Velagapudi and Virtanen, {K. A.} and E. Pirinen and Pietil{\"a}inen, {K. H.}",
year = "2018",
month = "4",
doi = "10.1038/ijo.2017.299",
language = "English",
volume = "42",
pages = "817--825",
journal = "International Journal of Obesity",
issn = "0307-0565",
publisher = "Nature Publishing Group",
number = "4",

}

Adipose tissue mitochondrial capacity associates with long-term weight loss success. / Jokinen, R.; Rinnankoski-Tuikka, R.; Kaye, S.; Saarinen, L.; Heinonen, S.; Myöhänen, M.; Rappou, E.; Jukarainen, S.; Rissanen, A.; Pessia, A.; Velagapudi, V.; Virtanen, K. A.; Pirinen, E.; Pietiläinen, K. H.

I: International Journal of Obesity, Vol. 42, Nr. 4, 04.2018, s. 817-825 .

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

TY - JOUR

T1 - Adipose tissue mitochondrial capacity associates with long-term weight loss success

AU - Jokinen, R.

AU - Rinnankoski-Tuikka, R.

AU - Kaye, S.

AU - Saarinen, L.

AU - Heinonen, S.

AU - Myöhänen, M.

AU - Rappou, E.

AU - Jukarainen, S.

AU - Rissanen, A.

AU - Pessia, A.

AU - Velagapudi, V.

AU - Virtanen, K. A.

AU - Pirinen, E.

AU - Pietiläinen, K. H.

PY - 2018/4

Y1 - 2018/4

N2 - OBJECTIVES:We investigated whether (1) subcutaneous adipose tissue (SAT) mitochondrial capacity predicts weight loss success and (2) weight loss ameliorates obesity-related SAT mitochondrial abnormalities.METHODS:SAT biopsies were obtained from 19 clinically healthy obese subjects (BMI 34.6±2.7 kg/m2) during a weight-loss intervention (0, 5, and 12 months) and from 19 lean reference subjects (BMI 22.7±1.1 kg/m2) at baseline. Based on one-year weight loss outcome, the subjects were divided into two groups: continuous weight losers (WL, n=6) and weight regainers (WR, n=13). Main outcome measures included SAT mitochondrial pathways from transcriptomics, mitochondrial amount (mitochondrial DNA (mtDNA), Porin protein levels), mtDNA-encoded transcripts, oxidative phosphorylation (OXPHOS) proteins, and plasma metabolites of the mitochondrial branched-chain amino acid catabolism (BCAA) pathway. SAT and visceral adipose tissue (VAT) glucose uptake was measured with positron emission tomography.RESULTS:Despite similar baseline clinical characteristics, SAT in the WL group exhibited higher gene expression level of nuclear-encoded mitochondrial pathways (P=0.0224 OXPHOS, P=0.0086 tricarboxylic acid cycle, P=0.0074 fatty acid beta-oxidation and P=0.0122 BCAA), mtDNA transcript COX1 (P=0.0229) and protein level of Porin (P=0.0462) than the WR group. Many baseline mitochondrial parameters correlated with weight loss success, and with SAT and VAT glucose uptake. During weight loss, the nuclear-encoded mitochondrial pathways were downregulated, together with increased plasma metabolite levels of BCAAs in both groups. MtDNA copy number increased in the WR group at 5 months (P=0.012), but decreased to baseline level between 5 to 12 months (P=0.015). The only significant change in the WL group for mtDNA was a reduction between 5 and 12 months (P=0.004). The levels of Porin did not change in either group upon weight loss.CONCLUSIONS:Higher mitochondrial capacity in SAT predicts good long-term weight loss success. Weight loss does not ameliorate SAT mitochondrial downregulation and based on pathway expression, may paradoxically further reduce it.DATA AVAILABILITY:The transcriptomics data generated in this study have been deposited to the Gene Expression Omnibus public repository, accession number GSE103769.

AB - OBJECTIVES:We investigated whether (1) subcutaneous adipose tissue (SAT) mitochondrial capacity predicts weight loss success and (2) weight loss ameliorates obesity-related SAT mitochondrial abnormalities.METHODS:SAT biopsies were obtained from 19 clinically healthy obese subjects (BMI 34.6±2.7 kg/m2) during a weight-loss intervention (0, 5, and 12 months) and from 19 lean reference subjects (BMI 22.7±1.1 kg/m2) at baseline. Based on one-year weight loss outcome, the subjects were divided into two groups: continuous weight losers (WL, n=6) and weight regainers (WR, n=13). Main outcome measures included SAT mitochondrial pathways from transcriptomics, mitochondrial amount (mitochondrial DNA (mtDNA), Porin protein levels), mtDNA-encoded transcripts, oxidative phosphorylation (OXPHOS) proteins, and plasma metabolites of the mitochondrial branched-chain amino acid catabolism (BCAA) pathway. SAT and visceral adipose tissue (VAT) glucose uptake was measured with positron emission tomography.RESULTS:Despite similar baseline clinical characteristics, SAT in the WL group exhibited higher gene expression level of nuclear-encoded mitochondrial pathways (P=0.0224 OXPHOS, P=0.0086 tricarboxylic acid cycle, P=0.0074 fatty acid beta-oxidation and P=0.0122 BCAA), mtDNA transcript COX1 (P=0.0229) and protein level of Porin (P=0.0462) than the WR group. Many baseline mitochondrial parameters correlated with weight loss success, and with SAT and VAT glucose uptake. During weight loss, the nuclear-encoded mitochondrial pathways were downregulated, together with increased plasma metabolite levels of BCAAs in both groups. MtDNA copy number increased in the WR group at 5 months (P=0.012), but decreased to baseline level between 5 to 12 months (P=0.015). The only significant change in the WL group for mtDNA was a reduction between 5 and 12 months (P=0.004). The levels of Porin did not change in either group upon weight loss.CONCLUSIONS:Higher mitochondrial capacity in SAT predicts good long-term weight loss success. Weight loss does not ameliorate SAT mitochondrial downregulation and based on pathway expression, may paradoxically further reduce it.DATA AVAILABILITY:The transcriptomics data generated in this study have been deposited to the Gene Expression Omnibus public repository, accession number GSE103769.

KW - 3121 Internal medicine

KW - 3111 Biomedicine

KW - 3124 Neurology and psychiatry

U2 - 10.1038/ijo.2017.299

DO - 10.1038/ijo.2017.299

M3 - Article

VL - 42

SP - 817

EP - 825

JO - International Journal of Obesity

JF - International Journal of Obesity

SN - 0307-0565

IS - 4

ER -